Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and abnormally elevated moods.[4][5][7] If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe, it is called hypomania.[4] During mania, an individual behaves or feels abnormally energetic, happy, or irritable.[4] Individuals often make impulsive decisions with little regard for the consequences.[5] There is usually a reduced need for sleep during manic phases.[5] During periods of depression, individuals may experience crying, a negative outlook on life, and poor eye contact with others.[4] The risk of suicide is high; over a period of 20 years 6% of people died by suicide, while 30-40% engaged in self-harm.[4] Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder.[4]

Mood stabilizers—lithium and certain anticonvulsants such as valproate and carbamazepine—are the mainstay of long-term relapse prevention.[12]Antipsychotics are given during acute manic episodes, as well as in cases where mood stabilizers are poorly tolerated or ineffective, or where compliance is poor.[12] There is some evidence that psychotherapy improves the course of this disorder.[13] The use of antidepressants in depressive episodes is controversial—they can be effective but have been implicated in triggering manic episodes.[14] However, the treatment of depressive episodes is often difficult.[12]Electroconvulsive therapy (ECT) is effective in acute manic and depressed episodes, especially with psychosis or catatonia.[lower-alpha 1][12] Admission to a psychiatric hospital may be required if a person is a risk to themselves or others; involuntary treatment is sometimes necessary if the affected person refuses treatment.[4]

Bipolar disorder occurs in approximately 1% of the global population.[12] In the United States, about 3% are estimated to be affected at some point in their life; rates appear to be similar in females and males.[6][16] The most common age at which symptoms begin is 25.[4] Around a quarter to a third of people with bipolar disorder have financial, social, or work-related problems due to the illness.[4] Bipolar disorder is among the top 20 causes of disability worldwide and leads to substantial costs for society.[17] Due to lifestyle choices and the side effects of medications, the risk of death from natural causes such as coronary heart disease in people with bipolar is twice that of the general population.[4]

Signs and symptoms

Bipolar mood shifts

Late adolescence and early adulthood are peak years for the onset of bipolar disorder.[18][19] The condition is characterized by intermittent episodes of mania or depression, with an absence of symptoms in between.[20] During these episodes, people with bipolar disorder exhibit disruptions in normal mood, psychomotor activity-the level of physical activity that is influenced by mood-(e.g., constant fidgeting with mania or slowed movements with depression), circadian rhythm, and cognition. Mania can present with varying levels of mood disturbance, ranging from euphoria that is associated with "classic mania" to dysphoria and irritability.[21] Psychotic symptoms such as delusions or hallucinations may occur in both manic and depressive episodes, their content and nature is consistent with the person's prevailing mood.[4]

According to the DSM-5 criteria, mania is distinguished from hypomania by length, as hypomania is present if elevated mood symptoms are present for at least four consecutive days, and mania is present if such symptoms are present for more than a week. Unlike mania, hypomania is not always associated with impaired functioning.[12] The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood.[22]

Manic episodes

Also known as a manic episode, mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to delirium. The core symptom of mania involves an increase in energy of psychomotor activity. Mania can also present with increased self-esteem or grandiosity, racing thoughts, pressured speech that is difficult to interrupt, decreased need for sleep, disinhibited social behavior,[21] increased goal-oriented activities and impaired judgment—exhibition of behaviors characterized as impulsive or high-risk, such as hypersexuality or excessive spending.[23][24][25] To meet the definition for a manic episode, these behaviors must impair the individual's ability to socialize or work.[23][25] If untreated, a manic episode usually lasts three to six months.[26]

In severe manic episodes, a person can experience psychotic symptoms, where thought content is affected along with mood.[25] They may feel unstoppable, or as if they have a special relationship with God, a great mission to accomplish, or other grandiose or delusional ideas.[27] This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital.[24][25] The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale, though questions remain about the reliability of these scales.[28]

Hypomanic episodes

An 1858 lithograph captioned 'Melancholy passing into mania'

Hypomania is the milder form of mania, defined as at least four days of the same criteria as mania,[25] but which does not cause a significant decrease in the individual's ability to socialize or work, lacks psychotic features such as delusions or hallucinations, and does not require psychiatric hospitalization.[23] Overall functioning may actually increase during episodes of hypomania and is thought to serve as a defense mechanism against depression by some.[32] Hypomanic episodes rarely progress to full-blown manic episodes.[32] Some people who experience hypomania show increased creativity[25][33] while others are irritable or demonstrate poor judgment.[10]

Hypomania may feel good to some persons who experience it, though most people who experience hypomania state that the stress of the experience is very painful.[25] Bipolar people who experience hypomania tend to forget the effects of their actions on those around them. Even when family and friends recognize mood swings, the individual will often deny that anything is wrong.[34] If not accompanied by depressive episodes, hypomanic episodes are often not deemed problematic, unless the mood changes are uncontrollable, or volatile.[32] Most commonly, symptoms continue for a few weeks to a few months.[35]

The earlier the age of onset, the more likely the first few episodes are to be depressive.[37] Since a diagnosis of bipolar disorder requires a manic or hypomanic episode, many affected individuals are initially misdiagnosed as having major depression and incorrectly treated with prescribed antidepressants.[38]

Mixed affective episodes

In bipolar disorder, a mixed state is an episode during which symptoms of both mania and depression occur simultaneously.[39] Individuals experiencing a mixed state may have manic symptoms such as grandiose thoughts while simultaneously experiencing depressive symptoms such as excessive guilt or feeling suicidal.[39] They are considered to have a higher risk for suicidal behavior as depressive emotions such as hopelessness are often paired with mood swings or difficulties with impulse control.[39]Anxiety disorders occur more frequently a comorbidity in mixed bipolar episodes than in non-mixed bipolar depression or mania.[39] Substance abuse (including alcohol) also follows this trend, thereby appearing to depict bipolar symptoms as no more than a consequence of substance abuse.[39]

Causes

The causes of bipolar disorder likely vary between individuals and the exact mechanism underlying the disorder remains unclear.[44] Genetic influences are believed to account for 73–93% of the risk of developing the disorder indicating a strong hereditary component.[10] The overall heritability of the bipolar spectrum has been estimated at 0.71.[45]Twin studies have been limited by relatively small sample sizes but have indicated a substantial genetic contribution, as well as environmental influence. For bipolar I disorder, the rate at which identical twins (same genes) will both have bipolar I disorder (concordance) is around 40%, compared to about 5% in fraternal twins.[23][46] A combination of bipolar I, II, and cyclothymia similarly produced rates of 42% and 11% (identical and fraternal twins, respectively).[45] The rates of bipolar II combinations without bipolar I are lower—bipolar II at 23 and 17%, and bipolar II combining with cyclothymia at 33 and 14%—, which may reflect relatively higher genetic heterogeneity.[45]

The cause of bipolar disorders overlaps with major depressive disorder. When defining concordance as the co-twins having either bipolar disorder or major depression, then the concordance rate rises to 67% in identical twins and 19% in fraternal twins.[47] The relatively low concordance between fraternal twins brought up together suggests that shared family environmental effects are limited, although the ability to detect them has been limited by small sample sizes.[45]

Although the first genetic linkage finding for mania was in 1969,[48] linkage studies have been inconsistent.[23] Findings point strongly to heterogeneity, with different genes implicated in different families.[49] Robust and replicable genome-wide significant associations showed several common single-nucleotide polymorphisms (SNPs) are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN.[40][50] The largest and most recent genome-wide association study failed to find any locus that exerts a large effect, reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.[50] Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially associated in a meta-analysis, but this association disappeared after correction for multiple testing.[51] On the other hand, two polymorphisms in TPH2 were identified as being associated with bipolar disorder.[52]

Environmental

Psychosocial factors play a significant role in the development and course of bipolar disorder, and individual psychosocial variables may interact with genetic dispositions.[57] Recent life events and interpersonal relationships likely contribute to the onset and recurrence of bipolar mood episodes, just as they do for unipolar depression.[58] In surveys, 30–50% of adults diagnosed with bipolar disorder report traumatic/abusive experiences in childhood, which is associated with earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as post-traumatic stress disorder.[59] The number of reported stressful events in childhood is higher in those with an adult diagnosis of bipolar spectrum disorder than in those without, particularly events stemming from a harsh environment rather than from the child's own behavior.[60] Acutely, mania can be induced by sleep deprivation in around 30% of people with bipolar disorder.[61]

Proposed mechanisms

Brain imaging studies have revealed differences in the volume of various brain regions between patients with bipolar disorder and healthy control subjects.

The precise mechanisms that cause bipolar disorder are not well understood. Bipolar disorder is thought to be associated with abnormalities in the structure and function of certain brain areas responsible for cognitive tasks and the processing of emotions.[20] A neurologic model for bipolar disorder proposes that the emotional circuitry of the brain can be divided into two main parts.[20] The ventral system (regulates emotional perception) includes brain structures such as the amygdala, insula, ventral striatum, ventral anterior cingulate cortex, and the prefrontal cortex.[20] The dorsal system (responsible for emotional regulation) includes the hippocampus, dorsal anterior cingulate cortex, and other parts of the prefrontal cortex.[20] The model hypothesizes that bipolar disorder may occur when the ventral system is overactivated and the dorsal system is underactivated.[20] Other models suggest the ability to regulate emotions is disrupted in people with bipolar disorder and that dysfunction of the ventricular prefrontal cortex (vPFC) is crucial to this disruption.[20]

Functional MRI findings suggest that the vPFC regulates the limbic system, especially the amygdala.[67] In people with bipolar disorder, decreased vPFC activity allows for dysregulated activity of the amygdala, which likely contributes to labile mood and poor emotional regulation.[67] Consistent with this, pharmacological treatment of mania returns vPFC activity to the levels in non-manic people, suggesting that vPFC activity is an indicator of mood state. However, while pharmacological treatment of mania reduces amygdala hyperactivity, it remains more active than the amygdala of those without bipolar disorder, suggesting amygdala activity may be a marker of the disorder rather than the current mood state.[68] Manic and depressive episodes tend to be characterized by dysfunction in different regions of the vPFC. Manic episodes appear to be associated with decreased activation of the right vPFC whereas depressive episodes are associated with decreased activation of the left vPFC.[67]

People with bipolar disorder who are in a euthymic mood state show decreased activity in the lingual gyrus compared to people without bipolar disorder.[20] In contrast, they demonstrate decreased activity in the inferior frontal cortex during manic episodes compared to people without the disorder.[20] Similar studies examining the differences in brain activity between people with bipolar disorder and those without did not find a consistent area in the brain that was more or less active when comparing these two groups.[20] People with bipolar have increased activation of left hemisphere ventral limbic areas—which mediate emotional experiences and generation of emotional responses—and decreased activation of right hemisphere cortical structures related to cognition—structures associated with the regulation of emotions.[69]

Neuroscientists have proposed additional models to try to explain the cause of bipolar disorder. One proposed model for bipolar disorder suggests that hypersensitivity of reward circuits consisting of frontostriatal circuits causes mania, and decreased sensitivity of these circuits causes depression.[70] According to the "kindling" hypothesis, when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start (and recur) spontaneously. There is evidence supporting an association between early-life stress and dysfunction of the hypothalamic-pituitary-adrenal axis leading to its overactivation, which may play a role in the pathogenesis of bipolar disorder.[71][72] Other brain components that have been proposed to play a role in bipolar disorder are the mitochondria[44] and a sodium ATPasepump.[73]Circadian rhythms and regulation of the hormone melatonin also seem to be altered.[74]

Dopamine, a neurotransmitter responsible for mood cycling, has increased transmission during the manic phase.[22][75] The dopamine hypothesis states that the increase in dopamine results in secondary homeostaticdownregulation of key system elements and receptors such as lower sensitivity of dopaminergic receptors. This results in decreased dopamine transmission characteristic of the depressive phase.[22] The depressive phase ends with homeostatic upregulation potentially restarting the cycle over again.[76]Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.[77]

Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-inositol levels, inhibition of cAMP signaling, and through altering subunits of the dopamine-associated G-protein.[78] Consistent with this, elevated levels of Gαi, Gαs, and Gαq/11 have been reported in brain and blood samples, along with increased protein kinase A (PKA) expression and sensitivity;[79] typically, PKA activates as part of the intracellular signalling cascade downstream from the detachment of Gαs subunit from the G protein complex.

Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2adrenergic receptors as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found.[80] One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder.[81]Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.[82]

Diagnosis

Bipolar disorder is commonly diagnosed during adolescence or early adulthood, but onset can occur throughout life.[5][83] Its diagnosis is based on the self-reported experiences of the individual, abnormal behavior reported by family members, friends or co-workers, observable signs of illness as assessed by a clinician, and ideally a medical work-up to rule-out other causes. Caregiver-scored rating scales, specifically from the mother, are more accurate than teacher and youth-scored reports in identifying youths with bipolar disorder.[84] Assessment is usually done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to oneself or others. The most widely used criteria for diagnosing bipolar disorder are from the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the World Health Organization's (WHO) International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10). The ICD-10 criteria are used more often in clinical settings outside of the U.S. while the DSM criteria are used within the U.S. and are the prevailing criteria used internationally in research studies. The DSM-5, published in 2013, includes further and more accurate specifiers compared to its predecessor, the DSM-IV-TR.[85] This work has influenced the upcoming eleventh revision of the ICD, which includes the various diagnoses within the bipolar spectrum of the DSM-V.[86]

Differential diagnosis

Mental disorders that can have symptoms similar to those seen in bipolar disorder include schizophrenia, major depressive disorder,[89] attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as borderline personality disorder.[90][91][92] A key difference between bipolar disorder and borderline personality disorder is the nature of the mood swings; in contrast to the sustained changes to mood over days to weeks or longer, those of the latter condition (more accurately called emotional dysregulation) are sudden and often short-lived, and secondary to social stressors.[93]

Bipolar spectrum

Since Emil Kraepelin's distinction between bipolar disorder and schizophrenia in the 19th century, researchers have defined a spectrum of different types of bipolar disorder.

Bipolar spectrum disorders include: bipolar I disorder, bipolar II disorder, cyclothymic disorder and cases where subthreshold symptoms are found to cause clinically significant impairment or distress.[5][83][86] These disorders involve major depressive episodes that alternate with manic or hypomanic episodes, or with mixed episodes that feature symptoms of both mood states.[5] The concept of the bipolar spectrum is similar to that of Emil Kraepelin's original concept of manic depressive illness.[95] Unipolar hypomania without accompanying depression has been noted in the medical literature.[96]

Criteria and subtypes

The DSM and the ICD characterize bipolar disorder as a spectrum of disorders occurring on a continuum. The DSM-5 and ICD-11 lists three specific subtypes:[5][86]

Bipolar I disorder: At least one manic episode is necessary to make the diagnosis;[99] depressive episodes are common in the vast majority of cases with bipolar disorder I, but are unnecessary for the diagnosis.[23] Specifiers such as "mild, moderate, moderate-severe, severe" and "with psychotic features" should be added as applicable to indicate the presentation and course of the disorder.[5]

Bipolar II disorder: No manic episodes and one or more hypomanic episodes and one or more major depressive episode.[99] Hypomanic episodes do not go to the full extremes of mania (i.e., do not usually cause severe social or occupational impairment, and are without psychosis), and this can make bipolar II more difficult to diagnose, since the hypomanic episodes may simply appear as periods of successful high productivity and are reported less frequently than a distressing, crippling depression.

Cyclothymia: A history of hypomanic episodes with periods of depression that do not meet criteria for major depressive episodes.[100]

When relevant, specifiers for peripartum onset and with rapid cycling should be used with any subtype. Individuals who have subthreshold symptoms that cause clinically significant distress or impairment, but do not meet full criteria for one of the three subtypes may be diagnosed with other specified or unspecified bipolar disorder. Other specified bipolar disorder is used when a clinician chooses to provide an explanation for why the full criteria were not met (e.g., hypomania without a prior major depressive episode).[5] If the condition is thought to have a non-psychiatric medical cause, the diagnosis of bipolar and related disorder due to another medical condition is made, while substance/medication-induced bipolar and related disorder is used if a medication is thought to have triggered the condition.[101]

Rapid cycling

Most people who meet criteria for bipolar disorder experience a number of episodes, on average 0.4 to 0.7 per year, lasting three to six months.[102]Rapid cycling, however, is a course specifier that may be applied to any bipolar subtype. It is defined as having four or more mood disturbance episodes within a one-year span. Rapid cycling is usually temporary but is common amongst people with bipolar disorder and affects between 25.8%–45.3% of them at some point in their life.[36][103] These episodes are separated from each other by a remission (partial or full) for at least two months or a switch in mood polarity (i.e., from a depressive episode to a manic episode or vice versa).[23] The definition of rapid cycling most frequently cited in the literature (including the DSM-V and ICD-11) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes during a 12-month period.[104] The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management.[105] People with the rapid cycling or ultradian subtypes of bipolar disorder tend to be more difficult to treat and less responsive to medications than other people with bipolar disorder.[106]

Children

Lithium is the only medication approved by the FDA for treating mania in children.

In the 1920s, Kraepelin noted that manic episodes are rare before puberty.[107] In general, bipolar disorder in children was not recognized in the first half of the twentieth century. This issue diminished with an increased following of the DSM criteria in the last part of the twentieth century.[107][108] The diagnosis of childhood bipolar disorder, while formerly controversial,[109] has gained greater acceptance among childhood and adolescent psychiatrists.[110] American children and adolescents diagnosed with bipolar disorder in community hospitals increased 4-fold reaching rates of up to 40% in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6%.[109] Studies using DSM criteria show that up to 1% of youth may have bipolar disorder.[107] The DSM-5 has established a diagnosis—disruptive mood dysregulation disorder—that covers children with long-term, persistent irritability that had at times been misdiagnosed as having bipolar disorder,[111] distinct from irritability in bipolar disorder that is restricted to discrete mood episodes.[110]

Elderly

Bipolar disorder is uncommon in older patients, with measured lifetime prevalence of 1% in over 60s and 12-month prevalence of 0.1 to 0.5% in people over 65. Despite this, it is overrepresented in psychiatric admissions, making up 4 to 8% of inpatient admission to aged care psychiatry units, and the incidence of mood disorders is increasing overall with the aging population. Depressive episodes more commonly present with sleep disturbance, fatigue, hopelessness about the future, slowed thinking, and poor concentration and memory; the last three symptoms are seen in what is known as pseudodementia. Clinical features also differ between those with late onset bipolar disorder and those who developed it early in life; the former group present with milder manic episodes, more prominent cognitive changes and have a background of worse psychosocial functioning, while the latter present more commonly with mixed affective episodes,[112] and have a stronger family history of illness.[113] Older people with bipolar disorder suffer cognitive changes, particularly in executive functions such as abstract thinking and switching cognitive sets, as well as concentrating for long periods and decision-making.[112]

Prevention

Attempts at prevention of bipolar disorder have focused on stress (such as childhood adversity or highly conflictual families) which, although not a diagnostically specific causal agent for bipolar, does place genetically and biologically vulnerable individuals at risk for a more severe course of illness.[114]

Medication

Lithium is often used to treat bipolar disorder and has the best evidence for reducing suicide.

Medications may differ depending on what episode is being treated.[12] The medication with the best overall evidence is lithium, which is an effective treatment for acute manic episodes, preventing relapses, and bipolar depression.[119] Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder.[120] Antipsychotics and mood stabilizers used together are quicker and more effective at treating mania than either class of drug used alone. Some analyses indicate antipsychotics alone are also more effective at treating acute mania.[12] Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.[106] It is unclear if ketamine (a common general dissociative anesthetic used in surgery) is useful in bipolar disorder.[121]

Mood stabilizers

Lithium and the anticonvulsantscarbamazepine, lamotrigine, and valproic acid are classed as mood stabilizers due to their effect on the mood states in bipolar disorder.[106] Lithium is preferred for long-term mood stabilization,[58] although it erodes kidney and thyroid function over extended periods.[12] Valproate has become a commonly prescribed treatment and effectively treats manic episodes.[122] A 2006 review found that haloperidol was an effective treatment for acute mania, limited data supported no difference in overall efficacy between haloperidol, olanzapine or risperidone, and that it could be less effective than aripiprazole.[123] Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or more symptoms similar to that of schizoaffective disorder. It is less effective in preventing relapse than lithium or valproate.[124][125] Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression.[126] It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder.[127] The effectiveness of topiramate is unknown.[128]

Antipsychotics

Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose.[58] Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers.[106]Olanzapine is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium.[129]

Antidepressants

Antidepressants are not recommended for use alone in the treatment of bipolar disorder and have not been found to be of any benefit over mood stabilizers.[12][130] Atypical antipsychotic medications (e.g., aripiprazole) are preferred over antidepressants to augment the effects of mood stabilizers due to the lack of efficacy of antidepressants in bipolar disorder.[106]

Other

Short courses of benzodiazepines are used in addition to other medications for calming effect until mood stabilizing become effective.[131]Electroconvulsive therapy (ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or catatonic features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder.[12]

Alternative medicine

Several studies have suggested that omega-3 fatty acids may have beneficial effects on depressive symptoms, but not manic symptoms. However, only a few small studies of variable quality have been published and there is not enough evidence to draw any firm conclusions.[133][134]

Prognosis

A lifelong condition with periods of partial or full recovery in between recurrent episodes of relapse,[36][133] bipolar disorder is considered to be a major health problem worldwide because of the increased rates of disability and premature mortality.[133] It is also associated with co-occurring psychiatric and medical problems, higher rates of death from natural causes (e.g., cardiovascular disease), and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment and contributing to poorer prognoses.[4][37] When compared to the general population, people with bipolar disorder also have higher rates of other serious medical comorbidities including diabetes mellitus, respiratory diseases, HIV, and Hepatitis C virus infection.[135] After a diagnosis is made, it remains difficult to achieve complete remission of all symptoms with the currently available psychiatric medications and symptoms often become progressively more severe over time.[87][136]

Compliance with medications is one of the most significant factors that can decrease the rate and severity of relapse and have a positive impact on overall prognosis.[137] However, the types of medications used in treating BD commonly cause side effects[138] and more than 75% of individuals with BD inconsistently take their medications for various reasons.[137] Of the various types of the disorder, rapid cycling (four or more episodes in one year) is associated with the worst prognosis due to higher rates of self-harm and suicide.[36] Individuals diagnosed with bipolar who have a family history of bipolar disorder are at a greater risk for more frequent manic/hypomanic episodes.[139] Early onset and psychotic features are also associated with worse outcomes,[140][141] as well as subtypes that are nonresponsive to lithium.[136]

Early recognition and intervention also improve prognosis as the symptoms in earlier stages are less severe and more responsive to treatment.[136] Onset after adolescence is connected to better prognoses for both genders, and being male is a protective factor against higher levels of depression. For women, better social functioning before developing bipolar disorder and being a parent are protective towards suicide attempts.[139]

Functioning

Changes in cognitive processes and abilities are seen in mood disorders, with those of bipolar disorder being greater than those in major depressive disorder.[142] These include reduced attentional and executive capabilities and impaired memory.[143] People with bipolar disorder often experience a decline in cognitive functioning during (or possibly before) their first episode, after which a certain degree of cognitive dysfunction typically becomes permanent, with more severe impairment during acute phases and moderate impairment during periods of remission. As a result, two-thirds of people with BD continue to experience impaired psychosocial functioning in between episodes even when their mood symptoms are in full remission. A similar pattern is seen in both BD-I and BD-II, but people with BD-II experience a lesser degree of impairment.[138] When bipolar disorder occurs in children, it severely and adversely affects their psychosocial development.[110] Children and adolescents with bipolar disorder have higher rates of significant difficulties with substance abuse, psychosis, academic difficulties, behavioral problems, social difficulties, and legal problems.[110] Cognitive deficits typically increase over the course of the illness. Higher degrees of impairment correlate with the number of previous manic episodes and hospitalizations, and with the presence of psychotic symptoms.[144] Early intervention can slow the progression of cognitive impairment, while treatment at later stages can help reduce distress and negative consequences related to cognitive dysfunction.[136]

Despite the overly ambitious goals that are frequently part of manic episodes, symptoms of mania undermine the ability to achieve these goals and often interfere with an individual's social and occupational functioning. One third of people with BD remain unemployed for one year following a hospitalization for mania.[145] Depressive symptoms during and between episodes, which occur much more frequently for most people than hypomanic or manic symptoms over the course of illness, are associated with lower functional recovery in between episodes, including unemployment or underemployment for both BD-I and BD-II.[5][146] However, the course of illness (duration, age of onset, number of hospitalizations, and presence or not of rapid cycling) and cognitive performance are the best predictors of employment outcomes in individuals with bipolar disorder, followed by symptoms of depression and years of education.[146]

Recovery and recurrence

A naturalistic study from first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status). However, 40% went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19% switched phases without recovery.[147]

Symptoms preceding a relapse (prodromal), specially those related to mania, can be reliably identified by people with bipolar disorder.[148] There have been intents to teach patients coping strategies when noticing such symptoms with encouraging results.[149]

Suicide

Bipolar disorder can cause suicidal ideation that leads to suicide attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide.[89] One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed.[40] The annual average suicide rate is 0.4%, which is 10–20 times that of the general population.[150] The number of deaths from suicide in bipolar disorder is between 18 and 25 times higher than would be expected in similarly aged people without bipolar disorder.[151] The lifetime risk of suicide has been estimated to be as high as 20% in those with bipolar disorder.[23]

Epidemiology

Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 1 to 3% in the general population.[6][152][153] However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8% of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5% have a hypomanic episode (the diagnostic threshold for bipolar II or cyclothymia). Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1% of the population, adding up to a total of 6.4%, were classified as having a bipolar spectrum disorder.[154] A more recent analysis of data from a second US National Comorbidity Survey found that 1% met lifetime prevalence criteria for bipolar I, 1.1% for bipolar II, and 2.4% for subthreshold symptoms.[155] Estimates vary about how many children and young adults have bipolar disorder.[110] These estimates range from 0.6 to 15% depending on differing settings, methods, and referral settings, raising suspicions of overdiagnosis.[110] One meta-analysis of bipolar disorder in young people worldwide estimated that about 1.8% of people between the ages of seven and 21 have bipolar disorder.[110] Similar to adults, bipolar disorder in children and adolescents is thought to occur at a similar frequency in boys and girls.[110]

There are conceptual and methodological limitations and variations in the findings. Prevalence studies of bipolar disorder are typically carried out by lay interviewers who follow fully structured/fixed interview schemes; responses to single items from such interviews may suffer limited validity. In addition, diagnoses (and therefore estimates of prevalence) vary depending on whether a categorical or spectrum approach is used. This consideration has led to concerns about the potential for both underdiagnosis and overdiagnosis.[156]

The incidence of bipolar disorder is similar in men and women[157] as well as across different cultures and ethnic groups.[158] A 2000 study by the World Health Organization found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available.[159] Within the United States, Asian Americans have significantly lower rates than their African and European American counterparts.[160] In 2017, the Global Burden of Disease Study estimated there were 4.5 million new cases and a total of 45.5 million cases globally.[161]

History

German psychiatrist Emil Kraepelin first distinguished between manic–depressive illness and "dementia praecox" (now known as schizophrenia) in the late 19th century.

Variations in moods and energy levels have been observed as part of the human experience throughout history. The words "melancholia", an old word for depression, and "mania" originated in Ancient Greece. The word melancholia is derived from melas (μέλας), meaning "black", and chole (χολή), meaning "bile" or "gall",[162] indicative of the term's origins in pre-Hippocratic humoral theory. Within the humoral theories, mania was viewed as arising from an excess of yellow bile, or a mixture of black and yellow bile. The linguistic origins of mania, however, are not so clear-cut. Several etymologies were proposed by the Ancient Roman physician Caelius Aurelianus, including the Greek word ania, meaning "to produce great mental anguish", and manos, meaning "relaxed" or "loose", which would contextually approximate to an excessive relaxing of the mind or soul.[163] There are at least five other candidates, and part of the confusion surrounding the exact etymology of the word mania is its varied usage in the pre-Hippocratic poetry and mythology.[163]

These concepts were developed by the German psychiatrist Emil Kraepelin (1856–1926), who, using Kahlbaum's concept of cyclothymia,[166] categorized and studied the natural course of untreated bipolar patients. He coined the term manic depressive psychosis, after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.[167]

The term "manic–depressive reaction" appeared in the first version of the DSM in 1952, influenced by the legacy of Adolf Meyer.[168] Subtyping into "unipolar" depressive disorders and bipolar disorders has its origin in Karl Kleist's concept – since 1911 – of unipolar and bipolar affective disorders, which was used by Karl Leonhard in 1957 to differentiate between unipolar and bipolar disorder in depression.[163] These subtypes have been regarded as separate conditions since publication of the DSM-III. The subtypes bipolar II and rapid cycling have been included since the DSM-IV, based on work from the 1970s by David Dunner, Elliot Gershon, Frederick Goodwin, Ronald Fieve, and Joseph Fleiss.[169][170][171]

Society and culture

Singer Rosemary Clooney's public revelation of bipolar disorder made her an early celebrity spokesperson for mental illness.

Cost

The economic costs of bipolar disorder to society are substantial. The United States spent approximately $202.1 billion on people diagnosed with bipolar disorder I (excluding other subtypes of bipolar disorder and undiagnosed people) in 2015.[135] One analysis estimated that the United Kingdom spent approximately £5.2 billion on the disorder in 2007.[173][174] In addition to the economic costs, bipolar disorder is a leading cause of disability and lost productivity worldwide.[17] People with bipolar disorder are generally more disabled, have a lower level of functioning, longer duration of illness, and increased rates of work absenteeism and decreased productivity when compared to people experiencing other mental health disorders.[175] The decrease in the productivity seen in those who care for people with bipolar disorder also significantly contributes to these costs.[176]

Advocacy

There are widespread issues with social stigma, stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder.[177] In 2000, actress Carrie Fisher went public with her bipolar disorder diagnosis. She became one of the most well-recognized advocates for people with bipolar disorder in the public eye and fiercely advocated to eliminate the stigma surrounding mental illnesses, including bipolar disorder.[178]Stephen Fried, who has written extensively on the topic, noted that Fisher helped to draw attention to the disorder's chronicity, relapsing nature, and that bipolar disorder relapses do not indicate a lack of discipline or moral shortcomings.[178] Since being diagnosed at age 37, actor Stephen Fry has pushed to raise awareness of the condition, with his 2006 documentary Stephen Fry: The Secret Life of the Manic Depressive.[179][180] In an effort to ease the social stigma associated with bipolar disorder, the orchestra conductor Ronald Braunstein cofounded the ME/2 Orchestra with his wife Caroline Whiddon in 2011. Braunstein was diagnosed with bipolar disorder in 1985 and his concerts with the ME/2 Orchestra were conceived in order to create a welcoming performance environment for his musical colleagues, while also raising public awareness about mental illness.[181][182]

Media portrayals

Several dramatic works have portrayed characters with traits suggestive of the diagnosis that has been the subject of discussion by psychiatrists and film experts alike. In Mr. Jones (1993), (Richard Gere) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome.[184] In The Mosquito Coast (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some paranoia.[185] Psychiatrists have suggested that Willy Loman, the main character in Arthur Miller's classic play Death of a Salesman, suffers from bipolar disorder.[186]

Creativity

A link between mental illness and professional success or creativity has been suggested, including in accounts by Socrates, Seneca the Younger, and Cesare Lombroso. Despite prominence in popular culture, the link between creativity and bipolar has not been rigorously studied. This area of study also is likely affected by confirmation bias. Some evidence suggests that some heritable component of bipolar disorder overlaps with heritable components of creativity. Probands of people with bipolar disorder are more likely to be professionally successful, as well as to demonstrate temperamental traits similar to bipolar disorder. Furthermore, while studies of the frequency of bipolar disorder in creative population samples have been conflicting, full-blown bipolar disorder in creative samples is rare.[192]

Research

Research directions for bipolar disorder in children include optimizing treatments, increasing the knowledge of the genetic and neurobiological basis of the pediatric disorder and improving diagnostic criteria.[109] Some treatment research suggests that psychosocial interventions that involve the family, psychoeducation, and skills building (through therapies such as CBT, DBT, and IPSRT) can benefit in addition to pharmocotherapy.[132]

See also

Notes

↑ Catatonia is a syndrome characterized by profound unresponsiveness or stupor with abnormal movements in a person who is otherwise awake.[15]

Related Research Articles

Bipolar I disorder is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other times, have one or more depressive episodes, and all experience a hypomanic stage before progressing to full mania.

Major depressive disorder (MDD), also known simply as depression, is a mental disorder characterized by at least two weeks of low mood that is present across most situations. It is often accompanied by low self-esteem, loss of interest in normally enjoyable activities, low energy, and pain without a clear cause. Those affected may also occasionally have false beliefs or see or hear things that others cannot. Some people have periods of depression separated by years in which they are normal, while others nearly always have symptoms present. Major depressive disorder can negatively affect a person's personal life, work life, or education as well as sleeping, eating habits, and general health. About 2–8% of adults with major depression die by suicide, and about 50% of people who die by suicide had depression or another mood disorder.

Mania, also known as manic syndrome, is a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together with lability of affect." Although mania is often conceived as a "mirror image" to depression, the heightened mood can be either euphoric or irritable; indeed, as the mania intensifies, irritability can be more pronounced and result in anxiety or violence.

Mood disorder, also known as mood affective disorders, is a group of conditions where a disturbance in the person's mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD).

Schizoaffective disorder is a mental disorder characterized by abnormal thought processes and an unstable mood. The diagnosis is made when the person has symptoms of both schizophrenia and a mood disorder—either bipolar disorder or depression—but does not meet the diagnostic criteria for schizophrenia or a mood disorder individually. The main criterion for the schizoaffective disorder diagnosis is the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Schizoaffective disorder can often be misdiagnosed when the correct diagnosis may be psychotic depression, psychotic bipolar disorder, schizophreniform disorder, or schizophrenia. It is imperative for providers to accurately diagnose patients, as treatment and prognosis differs greatly for each of these diagnoses.

Dysthymia, also known as persistent depressive disorder (PDD), is a mood disorder consisting of the same cognitive and physical problems as depression, but with longer-lasting symptoms. The concept was coined by Robert Spitzer as a replacement for the term "depressive personality" in the late 1970s.

A mixed affective state, formerly known as a mixed-manic or mixed episode, has been defined as a state wherein features unique to both depression and mania—such as despair, fatigue, morbid or suicidal ideation, racing thoughts, pressure of activity, and heightened irritability—occur either simultaneously or in very short succession.

The emphasis of the treatment of bipolar disorder is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms. Treatment methods include pharmacological and psychological techniques.

Cyclical variations in moods and energy levels have been recorded at least as far back as several thousand years. The words "melancholia" and "mania" have their etymologies in Ancient Greek. The word melancholia is derived from melas/μελας, meaning "black", and chole/χολη, meaning "bile" or "gall", indicative of the term's origins in pre-Hippocratic humoral theories. A man known as Aretaeus of Cappadocia has the first records of analyzing the symptoms of depression and mania in the 1st century of Greece. There is documentation that explains how bath salts were used to calm those with manic symptoms and also help those who are dealing with depression. Even today, lithium is used as a treatment to bipolar disorder which is significant because lithium could have been an ingredient in the Greek bath salt. Centuries passed and very little was studied or discovered. It wasn't until the mid-19th century that a French psychiatrist by the name of Jean-Pierre Falret wrote an article describing "circular insanity" and this is believed to be the first recorded diagnosis of bipolar disorder. Years later, in the early 1900s, Emil Kraepelin, a German psychiatrist, analyzed the influence of biology on mental disorders, including bipolar disorder. His studies are still used as the basis of classification of mental disorders today.

A spectrum disorder is a mental disorder that includes a range of linked conditions, sometimes also extending to include singular symptoms and traits. The different elements of a spectrum either have a similar appearance or are thought to be caused by the same underlying mechanism. In either case, a spectrum approach is taken because there appears to be "not a unitary disorder but rather a syndrome composed of subgroups". The spectrum may represent a range of severity, comprising relatively "severe" mental disorders through to relatively "mild and nonclinical deficits".

Bipolar disorder in children, or pediatric bipolar disorder (PBD), is a mental disorder in children and adolescents that, like bipolar disorder (BD) in adults, is characterized by extreme changes in mood and behavior accompanying periods of depressed or irritable moods and periods of elevated moods called manic or hypomanic episodes. These shifts are sometimes quick, but usually are gradual. The average age of onset of PBD is unclear, but the risk increases with the onset of puberty. PBD is typically more severe and has a poorer prognosis than BD with onset in late-adolescence or adulthood.

Bipolar II disorder is a bipolar spectrum disorder characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for bipolar II disorder requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder.

Cyclothymia, also known as cyclothymic disorder, is a mental disorder that involves numerous periods of symptoms of depression and periods of symptoms of hypomania. These symptoms, however, are not sufficient to be a major depressive episode or a hypomanic episode. Symptoms must last for more than one year in children and two years in adults.

The associated features of bipolar disorder are clinical phenomena that often accompany bipolar disorder (BD) but are not part of the diagnostic criteria for the disorder. There are several childhood precursors in children who later receive a diagnosis of bipolar disorder. They may show subtle early traits such as mood abnormalities, full major depressive episodes, and attention-deficit hyperactivity disorder. BD is also accompanied by changes in cognition processes and abilities. This includes reduced attentional and executive capabilities and impaired memory. How the individual processes the world also depends on the phase of the disorder, with differential characteristics between the manic, hypomanic and depressive states. Some studies have found a significant association between bipolar disorder and creativity.

The Hypomania Checklist (HCL-32) is a questionnaire developed by Dr. Jules Angst to identify hypomanic features in patients with major depressive disorder in order to help recognize bipolar II disorder and other bipolar spectrum disorders when people seek help in primary care and other general medical settings. It asks about 32 behaviors and mental states that are either aspects of hypomania or features associated with mood disorders. It uses short phrases and simple language, making it easy to read. The University of Zurich holds the copyright, and the HCL-32 is available for use at no charge. More recent work has focused on validating translations and testing whether shorter versions still perform well enough to be helpful clinically. Recent meta-analyses find that it is one of the most accurate assessments available for detecting hypomania, doing better than other options at recognizing bipolar II disorder.

The Mood Disorder Questionnaire (MDQ) is a self-report questionnaire designed to help detect bipolar disorder. It focuses on symptoms of hypomania and mania, which are the mood states that separate bipolar disorders from other types of depression and mood disorder. It has 5 main questions, and the first question has 13 parts, for a total of 17 questions. The MDQ was originally tested with adults, but it also has been studied in adolescents ages 11 years and above. It takes approximately 5–10 minutes to complete. In 2006, a parent-report version was created to allow for assessment of bipolar symptoms in children or adolescents from a caregiver perspective, with the research looking at youths as young as 5 years old. The MDQ has become one of the most widely studied and used questionnaires for bipolar disorder, and it has been translated into more than a dozen languages.

Hypomania is a mood state characterized by persistent disinhibition and mood elevation (euphoria), with behavior that is noticeably different from the person's typical behavior when in a non-depressed state. It may involve irritability, but less severely than full mania. According to DSM-5 criteria, hypomania is distinct from mania in that there is no significant functional impairment; mania, by DSM-5 definition, does include significant functional impairment and may have psychotic features.

The General Behavior Inventory (GBI) is a 73-question psychological self-report assessment tool designed by Richard Depue and colleagues to identify the presence and severity of manic and depressive moods in adults, as well as to assess for cyclothymia. It is one of the most widely used psychometric tests for measuring the severity of bipolar disorder and the fluctuation of symptoms over time. The GBI is intended to be administered for adult populations; however, it has been adapted into versions that allow for juvenile populations, as well as a short version that allows for it to be used as a screening test.

The following outline is provided as an overview of and topical guide to bipolar disorder:

Sleep is known to play an important role in the etiology and maintenance of a bipolar disorder. Patients with a bipolar disorder often have for example a less stable and more variable circadian activity. This circadian activity disruption is often also apparent, even if the person concerned isn't currently ill.

↑ Becker T, Kilian R (2006). "Psychiatric services for people with severe mental illness across western Europe: What can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care?". Acta Psychiatrica Scandinavica. 113 (429): 9–16. doi:10.1111/j.1600-0447.2005.00711.x. PMID16445476.

1 2 3 Montgomery P, Richardson AJ (April 2008). Montgomery P (ed.). "Omega-3 fatty acids for bipolar disorder". The Cochrane Database of Systematic Reviews (2): CD005169. doi:10.1002/14651858.CD005169.pub2. PMID18425912. Currently, there is simply not enough existing evidence, and what evidence is currently available is of such a varied and often questionable nature that no reliable conclusions may be drawn.

↑ Borch-Jacobsen M (October 2010). "Which came first, the condition or the drug?". London Review of Books. 32 (19): 31–33. Archived from the original on March 13, 2015. at the beginning of the 19th century with Esquirol's 'affective monomanias' (notably 'lypemania', the first elaboration of what was to become our modern depression)